1. Field of the Invention
This invention generally relates to cell migration inhibiting compositions and method and compositions for treating cancer. Certain embodiments relate to methods for identifying compositions that inhibit cell migration and methods for identifying compositions that have synergy with a chemotherapeutic agent.
2. Description of the Related Art
Abnormalities in how living cells move are the underlying cause of many human diseases. Cancer, heart disease, arteriosclerosis, wound healing, arthritis, and some autoimmune diseases all share common elements in that cell movement is perturbed. This change may be either accelerated or deficient cell movement.
Of the diseases caused by abnormal cell movement, cancer is the second leading cause of death in the United States. There have been approximately 16 million cancer cases diagnosed since 1990, and 5 million lives have been lost to cancer. 1 in 4 people in the United States will die of cancer. The American Cancer Society projects that 1,220,100 new cancer cases will be diagnosed in 2002 and that 552,200 Americans will die of cancer or more than 1500 people a day. These estimates exclude non-invasive cancers and do not include basal cell and squamous cell cancers. In fact, skin cancers are more common than cancers of any other organ, and over 1.3 million cases of basal cell and squamous cell skin cancer are expected to be diagnosed this year. The financial cost of cancer in the United States exceeds $100 billion per year.
Although the critical role of cell migration (invasion and metastasis) in cancer is recognized, the absence of technology for screening chemicals for effects on cell migration has left cell migration largely unexplored. Example of methods for studying cell migration include, for example, the Boyden Chamber Assay and the Scratch Wound Assay. The Boyden Chamber Assay generally involves placing cells on one side of a membrane. The membrane has pores of a diameter smaller than the diameter of the cells under investigation. After the cells are placed on one side of the membrane, the chamber is incubated for a period of time. Cell migration may be assessed by determining the number of cells that are present on the other side of the membrane after the period of time. The Scratch Wound Assay generally involves scraping a confluent monolayer of cells thereby creating a “wound” in the monolayer. Cell migration may be assessed by monitoring filling of the wound by surrounding cells. Another migration assay is commercially available from Chemicon International, Inc., Temecula, Calif. This assay generally involves dissociating migratory cells on the bottom of an insert membrane. The dissociated cells are lysed and detected using a dye that exhibits fluorescence when bound to cellular nucleic acids.
There are, however, several disadvantages to the above methods for studying cell migration. For example, these methods for studying cell migration are cumbersome, expensive, require relatively large amounts of reagents, insensitive, and are difficult to reproduce.